Phenylenediamines and process for preparing the same

ABSTRACT

Phenylenediamines represented by general formula (1): ##STR1## wherein R represents an alkyl group or an optionally substituted aralkyl group, X 1  represents a hydrogen atom or a halogen atom, and X 2  represents a halogen atom; salts thereof, and a process for preparing the same. The compounds are useful as intermediates for synthesis of pyridonecarboxylic acid derivatives useful as antibacterial agents.

TECHNICAL FIELD

The present invention relates to phenylenediamines useful asintermediates for synthesis of pyridonecarboxylic acid derivatives orsalts thereof which have excellent antibacterial action and can beabsorbed well when administered perorally, and to a process forpreparing the same.

BACKGROUND ART

Among compounds having a basic skeleton of pyridonecarboxylic acid therehave been known a variety of compounds useful as synthetic antibacterialagents, since they have excellent antibacterial activity and a wideantibacterial spectrum. Of these, in the clinical field, as therapeuticagents for infectious diseases there have been widely used compoundssuch as norfloxacin (Japanese Patent Application Laid-Open (kokai) No.53-141286), enoxacin (Japanese Patent Application Laid-Open (kokai) No.55-31042), ofloxacin (Japanese Patent Application Laid-Open (kokai) No.57-46986), ciprofloxacin (Japanese Patent Application Laid-Open (kokai)No. 58-76667), and tosufluoxacin (Japanese Patent Application Laid-Open(kokai) No. 60-228479).

However, these compounds are not perfectly satisfactory in terms ofantibacterial activity, intestinal absorption efficiency, stability inmetabolism, and side effects, inter alia, phototoxicity andcytotoxicity.

In view of the foregoing, an object of the present invention is toprovide pyridonecarboxylic acid-based antibacterial agents which havesatisfactory antibacterial activity, intestinal absorption efficiency,stability in metabolism, and acceptable side effects particularly interms of phototoxicity and cytotoxicity; and to provide intermediatesfor synthesis thereof.

DISCLOSURE OF THE INVENTION

The present inventors have conducted earnest studies in an attempt toobtain a compound which may serve as a clinically excellent syntheticantibacterial agent, and have found that pyridonecarboxilic acidsrepresented by the below-described formula (A) have excellentantibacterial activity to Gram-negative and -positive bacteria andremarkably low toxicity and are therefore suitable as syntheticantibacterial agents, and that the compounds (A) can be advantageouslyproduced on an industrial scale through a method in which reactionproceeds according to the below-described reaction scheme viaphenylenediamines represented by formula (1), leading to completion ofthe present invention. ##STR2## [wherein R¹ represents a lower alkylgroup; R² represents a hydrogen atom, a halogen atom, a hydroxy group, alower alkyl group, or an amino group; R³ represents a hydrogen atom or ahalogen atom; X¹ represents a hydrogen atom or a halogen atom; X²represents a halogen atom; Z represents a halogen atom or a saturatedcyclic amino group which may have substituents; A represents a nitrogenatom or --CY=(Y represents a hydrogen atom, a halogen atom, a loweralkyl group, or a lower alkoxy group); R represents an alkyl group or anaralkyl group which may have a substituent; R⁴ represents a lower alkoxygroup or a group of --N(R⁵)R⁶ (each of R⁵ and R⁶ represents a loweralkyl group); and L represents a halogen atom].

Briefly, an acrylate ester (C) and a phenylenediamine (1) are condensedand cyclized together to form a compound (B), from which theamino-protective group ( --COOR) is then removed, to thereby obtain acompound (A).

The phenylenediamine compounds (1) used in the reaction are novelcompounds; thus they are important intermediates for synthesis in thereaction.

Accordingly, the present invention provides phenylenediaminesrepresented by the above-described formula (1), salts thereof, and aprocess for preparing the same.

MODES FOR CARRYING OUT THE INVENTION

In the above-described formula (1), alkyl groups represented by Rpreferably have 1 to 18 carbon atoms. Specifically, mention may be givenof a methyl group, an ethyl group, an n-propyl group, an i-propyl group,an n-butyl group, an i-butyl group, linear or branched pentyl, hexyl,heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl,pentadecyl, hexadecyl, and octadecyl groups. Of these, those having 1 to6 carbon atoms are particularly preferred. Example aralkyl groupsrepresented by R include a benzyl group, a phenylethyl group, and aphenylpropyl group. Of these, the benzyl group is preferred. Examplehalogen atoms represented by X¹ or X² include a fluorine atom, achlorine atom, a bromine atom, and an iodine atom. X¹ is preferably ahydrogen atom or a fluorine atom, and X² is preferably a fluorine atomor a chlorine atom.

Example salts of phenylenediamines of formula (1) include salts withmineral acids such as HC1, salts with organic carboxylic acids such asformic acid and acetic acid, and salts with sulfonic acids such asmethanesulfonic acid and p-toluenesulfonic acid. Of these, preferredsalts are those with methanesulfonic acid and p-toluenesulfonic acid.

The phenylenediamines of formula (1) or their salts may exist not onlyin the non-solvated form but also as hydrates or solvates. Accordingly,the compounds of the present invention broadly encompass compounds inany crystal system, hydrates of the compounds, and solvates of thecompounds.

The compounds (1) of the present invention may be prepared by, forexample, the following reaction scheme. ##STR3## [wherein R, X¹, and X²have the same meanings as defined above].

Briefly, the benzoic acid derivative of formula (5) above is nitrated toobtain a nitrobenzoic acid derivative (4), and this derivative isazidated to form a compound (3). The compound (3) is reacted with analcohol represented by ROH so as to form a nitroaniline derivative (2),and reduction of nitroaniline derivative (2) produces a phenylenediamine(1).

Next, respective steps will be described in a step-by-step manner.

(1) Preparation of nitrobenzoic acid derivative (4):

Nitrobenzoic acid derivative (4) can be prepared by nitration ofcompound (5). Nitration may be carried out through use of any customarymethod generally employed for the nitration of aromatic compounds.Example nitration agents include nitric acid, an acid mixture in which anitrate and sulfuric acid are combined, and acetyl nitrate. The amountof the acid mixture to be used for the reaction is such that oneequivalent to a largely excessive amount of sulfuric acid or nitric acidis employed with respect to one equivalent of compound (5). The reactionis allowed to proceed by, for example, addition of compound (5) to theacid mixture. Preferably, the reaction temperature is -10° C. to 80° C.,and the reaction time is 5 minutes to 5 hours.

(2) Preparation of azide derivative (3)

Adization of compound (4) may be carried out by use of a method knownper se. For example, either one of the following methods (a) and (b) maybe used. (a) The carboxyl group is activated, followed by reaction withan azidation agent. (b) The carboxyl group is activated and hydrazine isreacted to form a hydrozide, followed by reaction with a nitrous acid.

In method (a), the carboxylic group of compound (4) may be activated byuse of an acid halide method or an acid mixture anhydride method. Apreferred acid halide is an acid chloride. In order to obtain an acidchloride of compound (4), compound (4) is preferably reacted with ahalogenation agent such as oxalyl chloride, phosphoryl chloride, thionylchloride, phosphorus pentachloride, or phosphorus trichloride. Thisreaction for obtaining an acid halide is preferably carried out, forexample, in a solvent such as methylene chloride at a temperaturebetween 0° C. and 100° C., preferably at about room temperature, for oneto 48 hours.

The acid mixture anhydride is preferably obtained by reacting compound(4) with ethyl chloroformate or a similar substance.

Example azidation agents to be reacted with the resultant acid halide oracid mixture anhydride include sodium azide and trimethylsilylazide.Azidation is preferably be carried out, for example, in a solvent suchas DMF at -20° to 20° C. for 5 minutes to 5 hours.

In the above-mentioned method (b), the thus-obtained acid halide or acidmixture anhydride is reacted with hydrazine hydrate at -20° to 20° C.,then with nitrous acid at -20° to 10° C. The reaction for obtaining thehydrazide derivative is preferably carried out, for example, in anethanol solvent for 5 minutes to 5 hours, whereas the reaction forobtaining the azide derivative is preferably carried out in an aqueoussolvent for 5 minutes to 5 hours.

(3) Preparation of nitroaniline derivative (2):

Nitroaniline derivative (2) is obtained through reaction between azidederivative (3) and the aforementioned alcohol ROH. Example alcoholswhich may be used include benzyl alcohol, ethanol, and2-methyl-2-propanol. Example solvents include benzyl alcohol, ethanol,2-methyl-2-propanol, methylene chloride, and DMF. The reactiontemperature is preferably between 0° C. and 100° C. and the reactiontime is 1-24 hours.

(4) Preparation of phenylenediamine (1)

Phenylenediamine (1) is prepared by subjecting the nitro group of thenitroaniline derivative (2) to a reduction process.

Reduction may be performed by a generally employed method. For example,there may be used a reduction method by use of dissolved metal, in whichzinc, iron, tin, tin chloride, etc. may be used in an acidic solution; areduction method making use of a sulfide such as sodium sulfide, sodiumhydrosulfide, or sodium dithionite; or a catalytic reduction methodmaking use of platinum, Raney nickel, platinum-black (Pt--C),palladium-carbon (Pd--C) or a similar substance.

Other than the above-mentioned methods, there may be used another methodin which nitroaniline derivative (2) is obtained by subjectingnitrobenzoic acid derivative (4) to a Hofmann rearrangement reaction.For example, nitrobenzoic acid derivative (4) is reacted with thionylchloride so as to form an acid chloride, and the acid chloride isreacted with ammonia to form an acid amide. The amide is then reactedwith hypobromous acid so as to obtain an isocyanate, followed byreaction with an alcohol, to thereby obtain nitroaniline derivative (2).The resultant nitroaniline derivative (2) is transformed into the targetphenylenediamine through reduction.

The thus-obtained phenylenediamine (1) may be further processed to formthe above-described salts or solvates, as needed.

As described above, through reaction with compound (C), condensation andcyclization, and deprotection, phenylenediamine (1) is transformed intopyridonecarboxylic acid derivatives which are useful antibacterialagents.

EXAMPLES

The present invention will next be described in detail by way ofexamples, which should not be construed as limiting the inventionthereto.

Example 1

(1) 2,3,4-Trifluoro-5-nitrobenzoic acid:

2,3,4-Trifluorobenzoic acid (1 g) was added to sulfuric acid (5 ml), andpotassium nitrate (630 mg) was gradually added to the mixture undercooling on ice. The resultant mixture was stirred overnight at roomtemperature, and the reaction mixture was poured onto crushed ice. Themixture was extracted with diethyl ether, and the organic phase wasdried over magnesium sulfate. The solvent was removed throughdistillation, and n-hexane was added to the residue, to thereby collectthe solid of the title compound (1 g) by filtration.

Form: colorless powder

Melting point: 127-135° C.

¹ H--NMR(CDC κ₃)δ; 8.67-8.71(m, 1H)

(2) N-Benzyloxycarbonyl-2,3,4-trifluoro-5-nitroaniline:

2,3,4-Trifluoro-5-nitrobenzoic acid (1 g) was added to methylenechloride (10 ml) and N,N-dimethylformamide (several ml), and oxalylchloride (1.2 ml) was added dropwise to the mixture. The resultantmixture was stirred overnight at room temperature, and the reactionmixture was concentrated under reduced pressure. Methylene chloride (10ml) and N,N-dimethylformamide (10 ml) were added to the resultantresidue, and sodium azide (322 mg) was added to the mixture undercooling on ice. The mixture was stirred at room temperature for onehour, and diethyl ether (20 ml), n-hexane (5 ml), and water (50 ml) wereadded to the reaction mixture, to thereby collect an organic phase,which was dried over magnesium sulfate. The solvent was removed throughdistillation, and toluene (10 ml) and benzyl alcohol (1 ml) were addedto the residue. The mixture was refluxed overnight. The reaction mixturewas concentrated under reduced pressure, and n-hexane was added to theresidue, to thereby collect the solid of the title compound (880 mg) byfiltration.

Form: yellow powder

Melting point: 136-145° C.

¹ H--NMR(CDC λ ₃)δ; 5.28(s, 2H), 6.96(brs, 1H), 7.36-7.45(m, 5H),8.75-8.86(m, 1H)

(3) N-benzyloxycarbonyl-2,3,4-trifluoro-m-phenylenediamine:

Iron (1.2 g) was added to ethanol (20 ml) and water (30 ml), and themixture was activated with concentrated hydrochloric acid (1 ml) andstirred at 60° C. with heat. A solution ofN-benzyloxycarbonyl-2,3,4-trifluoro-5-nitroaniline (800 mg) in ethanol(5 ml) was added dropwise to the above solution, and the mixture wasstirred at 80° C. for 10 minutes. The reaction mixture was filtered byuse of Celite, and the filtrate was concentrated under reduced pressure.The residue was subjected to column chromatography (silica gel 20g/n-hexane: ethyl acetate 1:1) for the target fractions, to therebyobtain the title compound (490 mg).

Form: yellow powder

¹ H--NMR(CDC λ ₃)δ; 5.19(s, 2H), 6.75(brs, 1H), 7.26-7.44(m, 6H)

Example 2

(1) 2,4-Difluoro-5-nitrobenzoic acid:

2,4-Difluoro-5-benzoic acid (151 g) was added to concentrated sulfuricacid (500 ml), and potassium nitrate (114 g) was added portionwisethereto over a period of 30 minutes while the mixture was stirred undercooling on ice. The resultant mixture was stirred for one hour, and thereaction mixture was poured onto crushed ice. The precipitate wascollected by filtration, washed with distilled water, and air-dried.Subsequently, the air-dried matter was further dried under reducedpressure over phosphorus pentoxide, to thereby obtain the title compound(164.5 g).

Form: colorless powder

Melting point: 125-130° C.

¹ H--NMR(CDC λ ₃)δ; 7.20(t, J=10 Hz, 1H), 8.90(t, J=8 Hz, 1H)

(2) N-tert-Butoxycarbonyl-2,4-difluoro-5-nitroaniline:

2,4-Difluoro-5-nitrobenzoic acid (50 g) was added to methylene chloride(400 ml) and N,N-dimethylformamide (several ml). Oxalyl chloride (63 ml)was added dropwise thereto. The resultant mixture was stirred overnightat room temperature, and the reaction mixture was concentrated underreduced pressure. Methylene chloride (80 ml) and N,N-dimethylformamide(90 ml) were added to the residue, and sodium azide (17.6 g) was addedportionwise to the mixture under cooling on ice. The mixture was stirredfor two hours, and 2-methyl-2-propanol (150 ml) was added to themixture. The resultant mixture was stirred for 2 hours at roomtemperature, overnight at 40° C., and for 4 hours at 70° C. Theresultant mixture was concentrated under reduced pressure, and ethylacetate was added to the residue, followed by washing with water twice.The washed matter was dried over magnesium sulfate and concentratedunder reduced pressure. Hexane was added to the residue, and throughfiltration, a solid of the title compound (47 g) was collected.

The filtrate was further concentrated under reduced pressure. Theresidue was subjected to column chromatography (silica gel 150g/chloroform) to thereby obtain the title compound (11.5 g). Thus, intotal 58.5 g of the title compound was obtained.

Form: yellow powder

Melting point: 87-91° C.

¹ H--NMR(CDC λ₃)ε; 1.54(s,9H), 6.72(brs,1H), 7.06(t,J=10 Hz, 1H),8.9-9.01(m,1H)

(3) N-tert-Butoxycarbonyl-2,4-difluoro-m-phenylenediamine:

N-tert-Butoxycarbonyl-2,4-difluoro-5-nitroaniline (20 g) was added tomethanol (500 ml) and acetic acid (20 ml). An acetic acid solution of10% palladium-on-carbon was added thereto, and the resultant mixture wasstirred overnight at room temperature in a stream of hydrogen. As thereaction had not been completed, the catalyst was replaced by freshcatalyst and stirring was continued for 2 days. Thereafter, the catalystwas exchanged with palladium-black, and the mixture was stirredovernight at room temperature. The catalyst was filtered off by use of amembrane filter. The filtrate was concentrated under reduced pressure,and ethyl acetate was added to the residue. The residue was washed witha solution of sodium bicarbonate. The washed matter was dried overmagnesium sulfate and concentrated under reduced pressure. The residuewas subjected to column chromatography (silica gel 150g/chloroform-ethyl acetate 10 1 ), (silica gel 150 g/chloroform-ethylacetate 20:1 ). Hexane was added to the residue, and a solid wascollected through filtration, to thereby obtain the title compound (9.2g).

Form: pale brown powder

Melting point: 114-121° C.

¹ H--NMR(CDCμ³)δ; 1.51(s,9H), 6.54(brs,1H), 6.78(t,J=11 Hz,1H),7.54-7.62(m,1H)

Example 3

N-Ethoxycarbonyl-2,4-difluoro-m-phenylenediamine methanesulfonate:

2,4-Difluoro-5-nitrobenzoic acid (6.1 g) was added to dichloromethane(20 ml), and oxalyl chloride (3 ml) and N,N-dimethylformamide (4 drops)were added thereto. The resultant mixture was stirred for 2 hours.Thereafter, the solvent and the excessive reagents were distilled offunder reduced pressure. The residue was dissolved in dichloromethane (6ml), and under stirring and cooling on ice, the resultant solution wasadded dropwise to sodium azide (2.1 g) in 5 ml of N,N-dimethylformamide.Stirring was continued for 10 minutes, and subsequently, at roomtemperature for 5 minutes. Diethyl ether (45 ml), n-hexane (15 ml) anddistilled water (100 ml) were added, and the resultant mixture wasshaken, to thereby separate the organic phase. The organic phase waswashed with distilled water (100 ml), dried over magnesium sulfate, andconcentrated under reduced pressure. Ethanol (6 ml) was added totwo-thirds of the residue. The mixture was heated in a water bath at 80°C. for 2 hours, to thereby obtain a crude solution ofN-ethoxycarbonyl-2,4-difluoro-5-nitroaniline in ethanol.

Ethanol (14 ml) was further added to the above-mentioned solution, andmethanesulfonic acid (2.0 g) and 10% palladium-on-carbon (200 mg) wereadded thereto. The resultant mixture was hydrogenated overnight at roomtemperature. The precipitate was dissolved by the addition of methanol(20 ml), and the catalyst was filtered off. The filtrate wasconcentrated under reduced pressure, and scales that precipitated werecollected through filtration. The scales were washed with a mixture ofethanol and diisopropyl ether, to thereby obtain 4.0 g of the titlecompound.

Form: fine red crystals

Example 4

N-Benzyloxycarbonyl-2,4-difluoro-m-phenylenediamine:

2,4-Difluoro-5-nitrobenzoic acid (20.3 g) was added to dichrolomethane(60 ml), and oxalyl chloride (10 ml) and N,N-dimethylformamide (15drops) were added thereto. The resultant mixture was stirred overnight,and the solvent and the excessive reagents were distilled off underreduced pressure. The residue was dissolved in dichloromethane (30 ml),and the mixture was added to N,N-dimethylformamide (15 ml). Understirring and cooling on ice, sodium azide (7.5 g) was added portionwiseto the mixture. Stirring was continued for 10 minutes, and subsequently,at room temperature for an additional 10 minutes. Diethyl ether (100ml), n-hexane (50 ml), and distilled water (400 ml) were added, and theresultant mixture was shaken, to thereby separate the organic phase. Theorganic phase was washed with distilled water twice, dried overanhydrous magnesium sulfate, and concentrated under reduced pressure.Benzyl alcohol (12.0 g) was added, and the mixture was concentratedunder reduced pressure. Toluene (150 ml) was added thereto. The mixturewas heated in a water bath at 40° C. for 2 hours, at 60° C. for 25hours, and at 100° C. for 1 hour. The solution matter was concentratedunder reduced pressure, so that it was gradually solidified. Thus, acrude N-benzyloxycarbonyl-2,4-difluoro-5-nitroaniline was obtained.

Iron powder (84 g) was added to a mixture of distilled water (300 ml)and ethanol (200 ml). Concentrated hydrochloric acid (7 ml) was addedportionwise to the mixture under stirring and heating at 80° C. andthereafter, the resultant mixture was stirred for 5 minutes.Subsequently, the entirety ofN-benzyloxycarbonyl-2,4-difluoro-5-nitroaniline mentioned above wasdissolved in ethanol (100 ml) and the solution was added portionwise sothat the mixture refluxed mildly. Thereafter, the resultant mixture wasstirred at 80° C. for 15 hours. Benzene (500 ml) was added thereto andthe mixture was stirred for 5 minutes. Iron powder was filtered off andthe filtrate was washed with ethanol. Distilled water (200 ml) was addedthereto and the mixture was shaken, to thereby separate the organicphase. The organic phase was dried over anhydrous magnesium sulfate andwhile passing through a thin layer of silica gel powder, concentratedunder reduced pressure. Colorless scales that precipitated weredispersed into diisopropyl ether. 18.2 g of the title compound wasobtained through filtration.

Form: pale brown powder

¹ H--NMR(CDCλ₃)δ; 5.20(s,2H), 6.75(brs,1H), 6.79(t,J=10 Hz,1H),7.30-7.48(m,5H), 7.54-7.68(m,1H)

Reference Example

(1) Ethyl1-(5-tert-butoxycarbonylamino-2,4-difluorophenyl)-8-chloro-6,7-difluoro-1,4-dihydro-4-oxoquinoline-3-carboxylate:

Ethyl 3-chloro-2,4,5-trifluorobenzoylacetate (23 g) was added toortho-ethyl formate (18.2 g) and acetic anhydride (25 g), and theresultant mixture was refluxed for 3 hours. After having being allowedto cool at room temperature, the mixture was concentrated under reducedpressure. Chloroform (120 ml) was added to the residue, andN-tert-butoxycarbonyl-2,4-difluoro-m-phenylenediamine (20 g) inchloroform-methanol was added dropwise thereto under cooling on ice.After the addition was finished, the resultant mixture was stirred atroom temperature for 2 hours. The reaction mixture was concentratedunder reduced pressure and hexane was added to the residue. A solid wascollected by filtration. Potassium carbonate (11 g) inN,N-dimethylformamide (100 ml) was added to the solid and the mixturewas stirred at room temperature for 2 hours. After having being allowedto cool at room temperature, the reaction mixture was poured onto icewater so as to collect precipitate. The precipitate was dissolved inchloroform, and washed with water. The washed matter was dried overmagnesium sulfate and subsequently, concentrated under reduced pressure.A solid was collected by filtration and washed with diethyl ether. As aresult, 26.1 g of the title compound was obtained.

Form: colorless powder

Melting point: 167-172° C.

¹ H-NMR(CDCλ₃)δ; 1.40(t,J=7 Hz,3H), 1.52(s,9H), 4.40(q,J=7 Hz,2H),6.80(brs,1H), 7.07(t,J=1 Hz,1H), 8.35(t,J=9 Hz,1H), 8.35(s,1H)

(2)1-(5-Amino-2,4-difluorophenyl)-8-chloro-6,7-difluoro-1,4-dihydro-4-oxoquinoline-3-carboxylicacid:

Ethyl1-(5-tert-butoxycarbonylamino-2,4-difluorophenyl)-8-chloro-6,7-difluoro-1,4-dihydro-4-oxoquinoline-3-carboxylate(26.1 g) was added to concentrated hydrochloric acid (150 ml) and aceticacid (90 ml) and the mixture was refluxed overnight under heating. Afterhaving being allowed to cool at room temperature, the precipitate wascollected through filtration, washed with ethanol, and further washedwith diethyl ether, to thereby obtain the title compound (18 g).

Form: pale yellow powder

Melting point: 225-226.5° C.

¹ H--NMR(d₆ -DMSO)λ; 7.09(t,J=8 Hz,1H), 7.43(t,J=1 Hz,1H), 8.40(t,J=9Hz, 1H), 8.69(s,1H)

(3)7-(3-Aminoazetidin-1-yl)-1-(5-amino-2,4-difluorophenyl)-8-chloro-6-fluoro-1,4-dihydro-4-oxoquinoline-3-carboxylicacid:

3-Aminoazetidine dihydrochloride (3.1 g) and N-methylpyrrolidine (6 g)were added to N,N-dimethylformamide (30 ml).1-(5-Amino-2,4-difluorophenyl)-8-chloro-6,7-difluoro-1,4-dihydro-4-oxoquinoline-3-carboxylicacid (6 g) was added to the mixture under stirring at 80° C. and themixture was further stirred for 4 hours. After having being allowed tocool at room temperature, ethanol was added to the mixture. Theprecipitate was collected through filtration, washed with ethanol, andsubsequently washed with diethyl ether, to thereby obtain the titlecompound (4 g).

Form: pale yellow powder

Melting point: >270° C.

¹ H--NMR(d₆ -DMSO)μ; 3.75(m, 1H), 4.10(m,2H), 4.66(m,2H), 5.43(brs,2H),6.97(t,J=8 Hz,1H), 7.36(t,J=11 Hz,1H), 7.87(d,J=14 Hz, 1H), 8.44(s,1H)

Industrial Applicability

The phenylenediamine compounds (1) of the present invention are usefulintermediates for synthesis of pyridonecarboxylic acid derivatives (A)which are useful as antibacterial agents and the like. By the process ofthe present invention, the phenylenediamine compounds (1) can beprepared advantageously.

We claim:
 1. A phenylenediamine represented by formula (1) or a saltthereof: ##STR4## wherein R represents an alkyl group or an aralkylgroup, X¹ represents a hydrogen atom or a halogen atom; and X²represents a halogen atom.
 2. A process for preparing a phenylenediaminerepresented by formula (1) or a salt thereof: ##STR5## wherein Rrepresents an alkyl group or an aralkyl group, X¹ represents a hydrogenatom or a halogen atom; and X² represents a halogen atom by reducing anitroaniline derivative of the following formula (2): ##STR6## whereinR, X¹, and X² have the same meanings as defined above.
 3. A process forpreparing a phenylenediamine represented by formula (1) or a saltthereof: ##STR7## wherein R represents an alkyl group or an aralkylgroup, X¹ represents a hydrogen atom or a halogen atom; and X²represents a halogen atom comprising the steps of:subjecting anitrobenzoic acid derivative of formula (4): ##STR8## wherein X¹ and X²have the same meanings as defined above to an azidation reaction so asto obtain a compound having the following formula (3): ##STR9## whereinX¹ and X² have the same meanings as defined above, then reacting theformula (3) compound with an alcohol of formula ROH (wherein Rrepresents an alkyl group or an aralkyl group which may havesubstituents) to thereby obtain a nitroaniline derivative of formula(2): ##STR10## wherein R, X¹, and X² have the same meanings as definedabove, and then reducing the formula (2) compound.
 4. A process forpreparing a phenylenediamine represented by formula (1) or a saltthereof: ##STR11## wherein R represents an alkyl group or an aralkylgroup, X¹ represents a hydrogen atom or a halogen atom; and X²represents a halogen atom comprising the steps of:subjecting a benzoicacid derivative of formula (5): ##STR12## wherein X¹ and X² have thesame meanings as defined above to a nitration reaction so as to obtain anitrobenzoic acid derivative of formula (4): ##STR13## wherein X¹ and X²have the same meanings as defined above, then subjecting the formula (4)nitrobenzoic acid derivative to an azidation reaction so as to obtain acompound having the following formula (3): ##STR14## wherein X¹ and X²have the same meanings as defined above, then reacting the formula (3)compound with an alcohol of formula ROH (wherein R represents an alkylgroup or an aralkyl group which may have substituents) to thereby obtaina nitroaniline derivative of formula (2): ##STR15## wherein R, X¹, andX² have the same meanings as defined above, and then reducing theformula (2) compound.